High-dose mitoxantrone in acute leukaemia: New York Medical College experience.
Based on promising preclinical data, a progressive series of evaluations of the use of high-dose mitoxantrone-based chemotherapy was initiated in acute leukaemia patients. A preliminary phase I study demonstrated that up to 80 mg/m2 of mitoxantrone in combination with cytarabine 3 g/m2 daily for 5 days could be given as induction therapy to leukaemic patients with acceptable toxicity. Pharmacokinetic data from these patients demonstrated that high concentrations of mitoxantrone were achievable in vivo to levels that were extremely cytotoxic in vitro. Subsequently, in a phase II study, 45 patients with untreated acute myelogenous leukaemia (AML) under the age of 60 received mitoxantrone 80 mg/m2 in combination with cytarabine 3 g/m2 daily for 5 days and etoposide 150 mg/m2 for 3 days. Following this induction, patients received five cycles of consolidation with cytarabine 3 g/m2 daily for 4 days with mitoxantrone 20 mg/m2 for 1 day on cycles 2 and 4, and etoposide 150 mg/m2 for 2 days with cytarabine on courses 1, 3 and 5. The patients in this study achieved a complete remission (CR) rate of 80% and a 3-year projected probability of survival of 40%. In a second AML study, 54 adults over the age of 60 with untreated AML were randomized to receive either high-dose or standard-dose mitoxantrone with cytarabine as a single induction regimen without consolidation. Patients receiving high-dose mitoxantrone did not experience increased morbidity or mortality compared with those given lower doses. Comparison of CR rates, disease-free and overall survival consistently favoured high-dose mitoxantrone, although the results did not achieve statistical significance. In patients with acute lymphocytic leukaemia (ALL), high-dose mitoxantrone with cytarabine was given as initial therapy in a phase II study involving 37 previously untreated adults. Results demonstrated that this dose-intensive regimen could produce a high CR rate (84%) with acceptable toxicity and compared favourably with experiences with vincristine/prednisone-based induction regimens. These studies demonstrate that high-dose mitoxantrone can be safely and effectively administered to patients with acute leukaemia and suggest that the incorporation of high doses of mitoxantrone into treatment regimens may lead to enhanced antileukaemic efficacy compared with standard doses. Phase III evaluations are planned.
Feldman
E J
EJ
New York Medical College, Valhalla, USA.
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D009518:New York
D000970:Antineoplastic Agents; D008942:Mitoxantrone